1. Field of the Invention
The present invention related to device for conducting immunoassay procedures. In particular, the invention relates to disposable, pre-packaged devices which are particularly suitable for conduct of diagnostic procedures based on immunological reactions at remote sites such as physician's offices and homes of users.
2. Description of the Prior Art
Since the important discovery of Millstein and Kohler reported in Nature 256: 495-497, 1975, the development of highly sensitive and specific immunoassay procedures has proceeded at a rapid pace. In fields such as clinical medicine, forensic sciences, environmental quality testing, food quality assurance, drug testing and other related areas, it has become possible to determine the presence and/or amount of trace substances in test samples even when such substances are present in very low concentrations in the order of parts per million, or even less. The development of non-radioactive labels or markers, such as enzyme color formers, has facilitated the use of immunoassay diagnostic procedures outside of laboratory settings and in remote sites such as physician's offices and even the homes of the users. In the physician's office, immunological procedures are useful to provide rapid, simple assays which may be performed while the patient is still in the office so that the diagnosis can be accomplished without delay and treatment instituted during a single visit. Without such simple assays, it has often been necessary for the physician to collect a sample from the patient during a first visit and to have the sample analyzed by a clinical laboratory with the results reported back to the physician by the laboratory at a later time. In the meanwhile, the patient was sent home and was required to return for a second visit with the physician in order to receive appropriate treatment and/or medication. Manifestly, such delay was inefficient and inappropriate and in some cases could even be life threatening.
Home testing has became desirable to facilitate testing by the consumer in the privacy of his or her own home. The results of such testing might, for example, indicate the necessity or lack of necessity of a visit to the physician. Examples of useful test for the "at home" market include tests for pregnancy, ovulation, streptococcus infection and other infections which are detectable by analysis of urine, saliva or other appropriate test samples.
For remote site testing, assuming appropriate sensitivity and specificity can be achieved, there are at least three other requirements for practical assay procedures. The first of these desirable factors is speed in that the assay must be performed in an acceptably short period of time, the shorter the better. Stability is also a desirable feature in that the components of the assay should be stable for an extended period of time without refrigeration or special handling and the assay results or readouts should be sufficiently stable so that the interpretation may be confirmed even several days after the initial test is performed. Finally, from a commercial view point it is desirable that the test be as simple as possible requiring only minimal or no instrumentation and precluding mistakes and poor performance resulting in incorrect interpretations.
Immunoassay kits employing enzyme markers are presently commercially available today for determining pregnancy and ovulation in the physician's office and in the home of the user. The technical components generally required in such kits are (1) a solid phase bearing immobilized antibody, (2) an enzyme labelled antibody, (3) a rinse solution (in some cases this may be the users tap water), and (4) a substrate for the enzyme. A typical procedure is that the sample is mixed with the solid phase and incubated (with or without a subsequent rinse step) and then the sample is discarded, the solid phase is then contacted with the enzyme labelled antibody and incubated. Thereafter the solid phase is rinsed and contacted by the substrate. After a period of time (ca 5 minutes) the color of the solid phase is observed. One such assay is described in U.S. Letters Pat. No. 4,632,901.
Enzyme labelled immunoassays are not without their own drawbacks resulting from the instability of some enzyme systems, the number of kit components and the complexity of the procedure. Such shortcomings have been addressed in the co-pending application of Cole, Davis and Sigillo, entitled "Metal Sol Capture Immunoassay Procedure, Kit For Use Therewith and Captured Metal Containing Composite," and filed Oct. 7, 1987, (serial number not yet assigned), which application is assigned to the assignee of the present application. In said co-pending Cole et al. application, a metal particle label is utilized and a collectible, solid phase, metal containing composite is formed. The composite is collected on a filter element or the like where the presence of analyte in the original sample is determined or detected by evaluating, through direct visual examination, the presence of metal in the collected solid phase composite.
One of the difficulties encountered in the development of test devices for remote site testing is the provision of a practical pre-packaged disposable device to facilitate efficient, relatively inexpensive test procedures. This, of course, requires a device which is inexpensive to construct, which has a shelf life appropriate to the commercial use of the device, which is protected against contamination during handling, and which may be simply and readily utilized when the appropriate time arises. The device illustrated in the '901 patent mentioned above addresses some of these problems and is available commercially; however, the device has a number of deficiencies including retarded flow of fluid into the absorbent. It is believed that such flow problems were perhaps alleviated to some degree by the provision of notched vertical venting grooves in the periphery of the absorbent plug. Such venting grooves facilitated venting of the device during use through small ports provided near the bottom of the container. Of course, liquid could escape through such vent ports creating a messy operation, sealing prior to use was difficult and the manufacture of the grooved absorbent plugs is a relatively expensive operation.
Other prior single test devices are illustrated in U.S. Letters Pat. Nos. 4,366,241 and 4,623,461. However, these devices are of limited application and also have excessive complexity.